中文摘要
支气管哮喘(简称哮喘)伴抑郁导致哮喘不易控制,是临床难治性哮喘的常见类型。我们的前期研究发现:哮喘伴抑郁患者CD4细胞具有特异的基因表达模式,CD4细胞功能紊乱可能是介导疾病发生的重要机制。本项研究拟在全基因组表达谱芯片检测与生物信息学分析基础上,筛选哮喘伴抑郁相关的特异性候选基因,进一步通过独立样本检测候选基因mRNA及其调控蛋白表达水平,明确候选基因与疾病状态的相关性,探讨哮喘伴抑郁特殊疾病表型的分子生物学基础,为建立新的临床治疗方案提供理论依据。
英文摘要
It has been proposed that depression or negative mood state often occurs at high frequencies in asthmatics, which is associated with poor asthma control or the occurrence of refractory asthma. Our previous study found that CD4 cells from asthmatics with depression has a specific pattern of gene expression, CD4 cell might play an important role in it. By using human whole genome microarray technology and bioinformatic analysis, gene expression profiles of asthmatics with or without depression were identified. This study aims to verify the differentially expressed genes found in our previous study and try to elucidate the underlying immunological mechanisms. In this study, expression levels of candidate genes mRNA and its regulatory protein will be detected, and their relationships with disease status will be explored meanwhile. This study will be beneficial for understanding the pathogenesis of asthma with depression and lay a foundation for establishment of new therapeutic approaches.
结题摘要
支气管哮喘患者抑郁发生率高于非哮喘人群,伴随抑郁导致哮喘不易控制,是临床难治性哮喘的常见类型。哮喘伴抑郁发病机理尚不清楚。该研究从CD4+ T 淋巴细胞各亚型免疫表型的角度研究哮喘伴负面情绪的发病机制,通过荧光定量PCR方法检测哮喘伴负面情绪患者,单纯哮喘患者和正常对照者外周血CD4+ T淋巴细胞中Th1/Th2/Th17相应转录因子 (T-bet/GATA-3/RORC)基因表达水平。通过Luminex液相芯片检测各组研究对象CD4+ T淋巴细胞Th细胞各亚型(Th1/Th2/Th17)相应细胞因子(IFN-γ/IL-4/IL-17)水平。发现哮喘伴负面情绪患者免疫分子表型为Th1、Th2共同激活,且二者保持平衡,伴随Th17激活。哮喘伴负面情绪患者相对单纯哮喘患者为Th1型异常激活。研究结果提示哮喘伴负面情绪的CD4+ T 淋巴细胞各亚型免疫表型与单纯哮喘患者表型存在差异,哮喘伴负面情绪拥有其独立的病理生理机制,为哮喘伴负面情绪的精准化治疗提供了依据。
